Secretory IgA antibodies at gastrointestinal and respiratory mucosal surfaces and in exocrine secretions appear to provide a potent first line of defense against a variety of bacterial, viral and Mycoplasma pathogens. The role that T-lymphocytes in mucosal tissue may play in modulating the course of infections is less well understood. In order to develop efficacious protective immunization procedures resulting in local mucosal immunity, we must better understand the basic processes leading to the generation of cellular and humoral mucosal immunity. We propose to study a number of animal model systems to determine the origins of sIgA precursor cells, their whereabouts when susceptible to antgen-driven clonal expansion, their migratory and tissue lodging characteristics and the cellular and humoral interactions which modulate the site and the extent of IgA atibody expression. Further, we propose to analyze the functional properties of effector T-lymphocytes in mucosal tissues and devise means to induce the presence of particular responding T-cells at local mucosal sites. Experimental approaches will include devising means to best present protective antigens and vaccines to stimulate a mucosal response. Further, the data from the experimental animal systems should provide a guide for devising ways to prime for a protective future secondary mucosal response and to elicit a rapid local protective secondary response when needed. Further, such factors as natural priming of mucosal responses and natural tolerization of certain aspects of mucosal responses by environmental antigens should be better appreciated through our experimental work and hence be more easily taken advantage of or circumvented when devising efficacious immunization procedures.